Noninvasive monitoring of changes in pancreatic beta-cell mass by bioluminescent imaging in MIP-luc transgenic mice.
We have generated a transgenic mouse model (MIP- LUC) that allows real-time imaging of insulin-secreting pancreatic beta cells in living mice. The beta cells of MIP- LUC transgenic mice emit a light signal that can be visualized externally by bioluminescent imaging using specialized equipment. In order to determine whether the intensity of the bioluminescent signal accurately reflects changes in beta-cell mass rather than simply transcriptional modulation of the mouse insulin I promoter-luciferase transgene, we examined the correlation between the bioluminescent signal and the beta-cell mass in MIP- LUC mice fed a regular or high-fat Western diet. Male MIP- LUC mice were fed a standard rodent diet (5% of calories from fat) or a high-fat Western diet (42% from fat) beginning at 4 weeks of age. The bioluminescent signal and beta-cell mass were measured after 6 and 10 weeks on each diet. The body weight, beta-cell mass, and bioluminescent signal increased with age and increased further in mice fed a high-fat diet. There was a statistically significant correlation between beta-cell mass and bioluminescent signal (r (2)=0.660, p=0.00137). Thus, in vivo bioluminescent imaging can be used to noninvasively monitor changes in beta-cell mass in living MIP- LUC mice, and it complements other approaches for monitoring beta-cell mass in states of insulin resistance, obesity, and diabetes.
Park
S-Y
SY
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. sooyoung@uchicago.edu
Bell
G I
GI
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D003952:Diagnostic Imaging / Q000379:methods*; D004036:Diet, Atherogenic; D005215:Fasting / Q000097:blood; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008991:Monitoring, Physiologic / Q000379:methods*; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology; D011401:Promoter Regions, Genetic; D019076:Transgenes
D001786:Blood Glucose; C514817:Ins1 protein, mouse; D007328:Insulin; D008156:Luciferases